Many of the metabolic processes associated with DNA are controlled by proteins which bind to specific DNA sites. The conformational aspects of these interactions are not understood. Two questions central to understanding these processes are; How do ligands discriminate between different base pair sequences? and How does one DNA region influence its adjacent region? In this proposal we wish to examine these questions using model systems. Raman spectroscopy will be used to investigate conformational aspects of the binding of netropsin and distamycin to DNA. These drugs show high specificity for AT base paired regions of DNA. Information on the sites on netropsin and distamycin which interact with DNA will be obtained from the Raman spectra of bound drug relative to its unbound spectra. Studies of molecular subunits of the drugs, together with theoretical vibrational analysis will be used to assign the Raman bands to specific molecular groups. The information obtained from this study will establish boundary conditions for calculating low energy conformation of drug-DNA complexes. An analysis of the Raman spectra of two block DNAs d(C15A15). d(T15G15) and d(C15A5).d(T5G15) and the polymers poly d(A).poly d(T) and poly d(G).poly d(C) will be made. This analysis should provide information about the conformation of the block DNA regions under different solvent conditions.